Lymphoma 1 Flashcards
What is lymphoma?
Neoplastic (malignant) tumour of lymphoid cells
Where are lymphomas usually found?
Lymph nodes, bone marrow and/or blood (lymphatic system)
Lymphoid organs; spleen or the gut-associated lymphoid tissue
Skin (often T cell disease)
What is the proportion of Hodgkin vs Non-Hodgkin lymphoma?
Non-Hodgkin Lymphoma - 80%
Hodgkin Lymphoma - 20%
What is the relationship between lymphomas and risk factors?
Most lymphoma subtypes/cases are sporadic with no known risk factors
Some lymphoma subtypes have specific risk factors - immune diseases acquired or iatrogenic, associated specific infections or inflammation
What is the reason for existing ‘limited’ DNA instability of lymphocytes?
For an adaptive immune response Generates immunoglobulin and T cell receptor diversity and Ig class switching
What happens to lymphocytes to generate antibody diversity?
Cut and recombined
Subjected to deliberate DNA mutagenesis (somatic hypermutation)
What is the benefit of rapid cell proliferation in the germinal centre?
Allows rapid response to infection
What is the downside to rapid cell proliferation in the germinal centre?
Rapid multiple cell divisions = increased chance of DNA replication errors
What is the benefit for lymphocytes being dependent on apoptosis?
Exquisite antibody specificity & eliminates self reactive clones
What is the downside to lymphocytes dependent on apoptosis?
Apoptosis is ‘switched off’ in germinal centre
Consequences of mutations in apoptosis regulating genes
What happens in the t(8;14) gene recombination error?
C-MYC oncogenes are located downstream of the IgH promoter (instead of the Ig Heavy chain gene) and are over expressed
What are the main groups/mechanisms of the risk factors for certain NHL subtypes?
Constant antigenic stimulation Viral infection (direct viral integration of lymphocytes) Loss of T cell function and EBV infection plus EBV infections of B cells
What can cause constant antigenic stimulation?
Bacterial infection (chronic) Auto immune disorders
What can cause loss of T cell function and EBV infection plus EBV infections of B cells?
Loss of T cells (untreated HIV infection)
Iatrogenic immunosuppression
What lymphoma can arise as a result of bacterial or auto immune antigenic drive?
B cell Non Hodgkin Lymphoma Marginal zone subtype (MZL)
Enteropathy associated T-Cell Non Hodgkin lymphoma (EATL)
What bacterial infections can cause MZL?
H. pylori - Gastric MALT (mucosa associated lymphoid tissue, MZL of stomach)
Sjogren syndrome (MZL of salivary glands
Hashimoto’s (MZL of thyroid)
What can cause EATL?
Coeliac disease/Gluten: small intestine EATL
What is an example of direct viral integration and lymphomagenesis?
HTLV1 retrovirus infects T cells by vertical transmission
What infection is associated with loss of T cell function lymphoma?
EBV infection
What are the elements of the lymphoreticular system?
Generative LR tissue
Reactive LR tissue
Acquired LR tissue
Give examples of generative lymphoreticular tissue and their function
Bone marrow and thymus
Generation/maturation of lymphoid cells
Give examples and function of reactive lymphoreticular tissue
Lymph nodes and spleen
Development of immune reaction
Give examples and function of acquired lymphoreticular tissue
Extranodal lymphoid tissue e.g. skin, stomach, lungs
Development of local immune reaction
Summarise the role of B cells
Express surface immunoglobulin
Antibody production
Summarise the role of T lymphocytes
Express surface T cell receptor
Regulation of B cells and macrophage function
Cytotoxic function
What can be found in the mantle zone of the lymphoid follicle?
Naïve unstimulated B cells
What can be found in the germinal centre of the lymphoid follicle?
B cells
Antigen presenting cells
What comprises the T cell area?
T cells
Antigen presenting cells
High endothelial vessels
How are types of lymphocytes detected?
Detected in tissue samples using immunohistochemistry
Identify subtypes and different stages of development by the different types of cell surface receptors expressed by the cells
Define lymphoma
Neoplastic proliferation of lymphoid cells forming discrete tissue masses
What is the site of lymphoma?
Arise in and involve lymphoid tissues (including acquired lymphoid tissue - extranodal lymphomas)
What are the various pathogenic causes of lymphoma?
Inherent instability of lymphoid cells
Inherited disorders increasing instability
Viral agents (EBV, HTLV-1)
Environmental agents (mutagens, chronic immune stimulation)
Iatrogenic causes (chemotherapy, radiotherapy)
What are the types of Hodgkin lymphoma?
Classical
Lymphocyte predominant
Which cell type stains CD20?
B cell
Give examples of low grade B cell Non-Hodgkin lymphomas
Follicular lymphoma
Small lymphocytic lymphoma / chronic lymphocytic leukaemia
Marginal zone lymphoma
Give examples of high grade B cell non-Hodgkin lymphoma
Diffuse large B cell lymphoma
Burkitt’s lymphoma
Give an example of an aggressive B cell Non-Hodgkin lymphoma
Mantle cell lymphoma
Which cell type stains CD3 and CD5?
T cell
How does follicular lymphoma present?
Disease of middle age/elderly
Lymphadenopathy
What is the histopathology of follicular lymphoma?
Follicular pattern
Germinal centre cell origin CD10, bcl-6+
What are the molecular features of follicular lymphoma?
14;18 translocation involving bcl-2 gene
How do you make an immunohistochemical diagnosis of follicular lymphoma?
Detection of bcl-2
What are the clinical features of small lymphocytic lymphoma / CLL?
Middle age / elderly
Nodes - lymphadenopathy, or blood - high white count
What is the histopathology of small lymphocytic lymphoma / CLL?
Small lymphocytes, naïve or post-germinal centre memory B cell
CD5, CD23+
What do you call the transformation of small lymphocytic lymphoma / CLL to high grade lymphoma?
Richter transformation
Where and why does marginal zone lymphoma arise?
Extranodal sites (gut, lung spleen) in response to chronic antigen stimulation
What are the clinical features of mantle cell lymphoma?
Middle age, male predominance
Lymph nodes, GI tract
Disseminated disease at presentation
What is the histopathology of mantle cell lymphoma?
Located in mantle zone
Pre-germinal centre cell
Aberrant CD5, cyclin D1 expression
What are the molecular features of mantle cell lymphoma?
11;14 translocation
Cyclin D1 over expression
What are the clinical features of Burkitt’s lymphoma?
Jaw or abdominal mass children/young adults
Endemic, sporadic, immunodeficiency
EBV associated
What is the histopathology of Burkitt’s lymphoma?
Germinal cell centre origin
Starry sky appearance
What are the molecular features of Burkitt’s lymphoma?
C-myc translocation (8:14, 2:8, 8;22)
What are the clinical features of diffuse large B cell lymphoma?
Middle age / elderly
Lymphadenopathy
What is the histopathology of diffuse large B cell lymphoma?
Germinal centre or post-germinal centre B cell
Sheets of large lymphoid cells
Germinal centre phenotype = good prognosis
P53 positive, high proliferation fraction = poor prognosis
What are the features of peripheral T cell lymphoma?
MA / elderly Lymphadenopathy and extranodal sites Large T lymphocytes Often with associated reactive cell population, esp eosinophils Aggressive
What are the clinical features of anaplastic large cell lymphoma?
Children / young adults
Lymphadenopathy
What are the histopathology features of anaplastic large cell lymphoma?
Large epithelioid lymphocytes
T cell or null phenotype
What are the molecular features of anaplastic large cell lymphoma?
2;5 translocation
Alk-1 protein expression
What are the subtypes of classical Hodgkin’s lymphoma?
Nodular sclerosing
Mixed cellularity
Lymphocyte rich and lymphocyte depleted
What are the clinical features of classical HL?
Young and MA
Often involves just single lymph node group
What are some key features of classical HL?
Thought to be germinal centre/post-germinal centre B cell origin
EBV associated
CD30+, CD15+, CD20-
What is the histopathology of classical HL?
Sclerosis, mixed cell population in which Reed-Sternberg and Hodgkin cells with eosinophils
What is the key clinical feature of nodular LP Hodgkins Lymphoma?
Isolated lymphadenopathy
What are some other features of nodular LP Hodgkins Lymphoma?
Germinal centre B cell (positive for some germinal centre B cell markers)
No association with EBV
CD20+, CD30-, CD15-
Indolent, can transform to high grade B cell lymphoma
What is the histopathology of nodular LP Hodgkins lymphoma?
B cell rich nodules with scattered L&H cells
